Anjali Desai1, Ying Zhao, Jeffrey S Warren. 1. Department of Pathology, University of Michigan Medical School, 1301 Catherine Street, Ann Arbor, MI 48109-0602, USA. desai@med.umich.edu
Abstract
BACKGROUND: Since its creation in 1992 by gene inactivation via gene targeting, the apolipoprotein E "knockout" mouse has become the most widely used rodent model for the study of atherosclerosis. Commercially available apolipoprotein E(-/-) mice are bred on a C57BL/6J background. The goal of the present study was to investigate the development of atherosclerosis in apolipoprotein E-deficient mice generated on a Balb/c background. METHODS: We compared serum cholesterol concentrations and the development of atherosclerotic lesions in heterozygous Balb/c [apolipoprotein E(+/-)] mice fed regular rodent chow, Balb/c apolipoprotein E-deficient mice fed regular chow, and Balb/c apolipoprotein E-deficient mice fed a high-fat diet for up to 30 weeks. Expression of the chemokine JE (murine homologue of MCP-1), as well as the adhesion molecules E-selectin, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1, in the aortas of knockout mice fed a high-fat diet was measured by enzyme-linked immunosorbent assay. RESULTS: Balb/c apolipoprotein E-deficient mice develop atherosclerotic lesions in a reproducible temporal and morphological pattern. Total serum cholesterol concentrations in Balb/c apolipoprotein E-deficient mice fed regular chow or a high-fat diet, respectively, closely parallel those reported for C57BL/6J apolipoprotein E-deficient mice. The expression of all three adhesion molecules in the aorta follows a similar temporal pattern, peaking in the first 15 weeks, whereas JE concentrations peak around 23 weeks. CONCLUSION: The availability of Balb/c apolipoprotein E-deficient mice will facilitate the study of atherosclerosis in a mouse strain that can concomitantly develop other pathological states that are not readily inducible in mice with the C57BL/6J background.
BACKGROUND: Since its creation in 1992 by gene inactivation via gene targeting, the apolipoprotein E "knockout" mouse has become the most widely used rodent model for the study of atherosclerosis. Commercially available apolipoprotein E(-/-) mice are bred on a C57BL/6J background. The goal of the present study was to investigate the development of atherosclerosis in apolipoprotein E-deficient mice generated on a Balb/c background. METHODS: We compared serum cholesterol concentrations and the development of atherosclerotic lesions in heterozygous Balb/c [apolipoprotein E(+/-)] mice fed regular rodent chow, Balb/c apolipoprotein E-deficient mice fed regular chow, and Balb/c apolipoprotein E-deficient mice fed a high-fat diet for up to 30 weeks. Expression of the chemokine JE (murine homologue of MCP-1), as well as the adhesion molecules E-selectin, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1, in the aortas of knockout mice fed a high-fat diet was measured by enzyme-linked immunosorbent assay. RESULTS: Balb/c apolipoprotein E-deficient mice develop atherosclerotic lesions in a reproducible temporal and morphological pattern. Total serum cholesterol concentrations in Balb/c apolipoprotein E-deficient mice fed regular chow or a high-fat diet, respectively, closely parallel those reported for C57BL/6J apolipoprotein E-deficient mice. The expression of all three adhesion molecules in the aorta follows a similar temporal pattern, peaking in the first 15 weeks, whereas JE concentrations peak around 23 weeks. CONCLUSION: The availability of Balb/c apolipoprotein E-deficient mice will facilitate the study of atherosclerosis in a mouse strain that can concomitantly develop other pathological states that are not readily inducible in mice with the C57BL/6J background.